This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. RNA interference (RNAi) is a conserved mechanism of eukaryotic gene silencing and regulation. In humans RNAi and the related micro-RNA pathways are carried out by a family of large, related protein complexes, generically termed RNA induced silencing complexes (RISCs). The goal of this work is to determine molecular structures of the various forms of RISC in an effort to better understand the mechanism of gene silencing by RNAi.